16-75529432-G-A

Variant names:

• chr16-75529432-G-A
• rs3826107
• NM_024533.5:c.953C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024533.5(CHST5):​c.953C>T​(p.Thr318Met) variant causes a missense change. The variant allele was found at a frequency of 0.183 in 1,612,534 control chromosomes in the GnomAD database, including 28,588 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T318R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.17 (2330 hom., cov: 33)
  • Exomes 𝑓: 0.18 (26258 hom.)
• Consequence: CHST5 NM_024533.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32
• Publications: 26 publications found

Genes affected

CHST5 (HGNC:1973): (carbohydrate sulfotransferase 5) The protein encoded by this gene belongs to the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family, members of which catalyze the transfer of sulfate to position 6 of galactose (Gal), N-acetylgalactosamine (GalNAc), or N-acetylglucosamine (GlcNAc) residues within proteoglycans, and sulfation of O-linked sugars of mucin-type acceptors. Carbohydrate sulfation plays a critical role in many biologic processes. This gene is predominantly expressed in colon and small intestine. [provided by RefSeq, Aug 2011]

ENSG00000260092 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019461811).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024533.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST5	NM_024533.5	MANE Select	c.953C>T	p.Thr318Met	missense	Exon 4 of 4	NP_078809.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST5	ENST00000336257.8	TSL:1 MANE Select	c.953C>T	p.Thr318Met	missense	Exon 4 of 4	ENSP00000338783.3	Q9GZS9-1
	ENSG00000260092	ENST00000460606.1	TSL:1	n.*1052C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000457544.1	H3BUA1
	ENSG00000260092	ENST00000460606.1	TSL:1	n.*1052C>T		3_prime_UTR	Exon 5 of 5	ENSP00000457544.1	H3BUA1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25806 AN: 152120 Hom.: 2328 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.163 AC: 40433 AN: 248110 AF XY: 0.164

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0962

Gnomad ASJ exome AF: 0.0924

Gnomad EAS exome AF: 0.176

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.185 AC: 270075 AN: 1460296 Hom.: 26258 Cov.: 34 AF XY: 0.183 AC XY: 132922 AN XY: 726504

African (AFR) AF: 0.115 AC: 3858 AN: 33474

American (AMR) AF: 0.101 AC: 4536 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 2522 AN: 26124

East Asian (EAS) AF: 0.189 AC: 7495 AN: 39686

South Asian (SAS) AF: 0.0913 AC: 7876 AN: 86254

European-Finnish (FIN) AF: 0.216 AC: 11309 AN: 52316

Middle Eastern (MID) AF: 0.132 AC: 763 AN: 5768

European-Non Finnish (NFE) AF: 0.199 AC: 221332 AN: 1111610

Other (OTH) AF: 0.172 AC: 10384 AN: 60364

GnomAD4 genome AF: 0.170 AC: 25819 AN: 152238 Hom.: 2330 Cov.: 33 AF XY: 0.168 AC XY: 12493 AN XY: 74416

African (AFR) AF: 0.122 AC: 5086 AN: 41558

American (AMR) AF: 0.144 AC: 2202 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 333 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1040 AN: 5182

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4828

European-Finnish (FIN) AF: 0.218 AC: 2314 AN: 10600

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13741 AN: 67988

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.187 Hom.: 7483

Bravo AF: 0.162

TwinsUK AF: 0.201 AC: 747

ALSPAC AF: 0.196 AC: 756

ESP6500AA AF: 0.122 AC: 537

ESP6500EA AF: 0.198 AC: 1701

ExAC AF: 0.166 AC: 20161

Asia WGS AF: 0.176 AC: 608 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.3
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.025	D
Sift4G	Benign	0.078	T
Polyphen		1.0	D
Vest4		0.18
MPC		1.5
ClinPred		0.025	T
GERP RS		2.8
Varity_R		0.34
gMVP		0.80
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3826107; hg19: chr16-75563330; COSMIC: COSV60337107; COSMIC: COSV60337107;